M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, Russia.
Medical Institute, Peoples' Friendship University of Russia, 117198 Moscow, Russia.
Int J Mol Sci. 2022 Feb 24;23(5):2499. doi: 10.3390/ijms23052499.
With the growing problem of the emergence of antibiotic-resistant bacteria, the search for alternative ways to combat bacterial infections is extremely urgent. While analyzing the effect of antimicrobial peptides (AMPs) on immunocompetent cells, their effect on all parts of the immune system, and on humoral and cellular immunity, is revealed. AMPs have direct effects on neutrophils, monocytes, dendritic cells, T-lymphocytes, and mast cells, participating in innate immunity. They act on B-lymphocytes indirectly, enhancing the induction of antigen-specific immunity, which ultimately leads to the activation of adaptive immunity. The adjuvant activity of AMPs in relation to bacterial and viral antigens was the reason for their inclusion in vaccines and made it possible to formulate the concept of a "defensin vaccine" as an innovative basis for constructing vaccines. The immunomodulatory function of AMPs involves their influence on cells in the nearest microenvironment, recruitment and activation of other cells, supporting the response to pathogenic microorganisms and completing the inflammatory process, thus exhibiting a systemic effect. For the successful use of AMPs in medical practice, it is necessary to study their immunomodulatory activity in detail, taking into account their pleiotropy. The degree of maturity of the immune system and microenvironment can contribute to the prevention of complications and increase the effectiveness of therapy, since AMPs can suppress inflammation in some circumstances, but aggravate the response and damage of organism in others. It should also be taken into account that the real functions of one or another AMP depend on the types of total regulatory effects on the target cell, and not only on properties of an individual peptide. A wide spectrum of biological activity, including direct effects on pathogens, inactivation of bacterial toxins and influence on immunocompetent cells, has attracted the attention of researchers, however, the cytostatic activity of AMPs against normal cells, as well as their allergenic properties and low stability to host proteases, are serious limitations for the medical use of AMPs. In this connection, the tasks of searching for compounds that selectively affect the target and development of an appropriate method of application become critically important. The scope of this review is to summarize the current concepts and newest advances in research of the immunomodulatory activity of natural and synthetic AMPs, and to examine the prospects and limitations of their medical use.
随着抗生素耐药菌出现问题的日益严重，寻找替代方法来对抗细菌感染变得极其紧迫。在分析抗菌肽 (AMPs) 对免疫活性细胞的作用时，揭示了它们对免疫系统的所有部分以及体液和细胞免疫的影响。AMPs 对中性粒细胞、单核细胞、树突状细胞、T 淋巴细胞和肥大细胞有直接作用，参与固有免疫。它们间接地对 B 淋巴细胞起作用，增强了对抗原特异性免疫的诱导，最终导致适应性免疫的激活。AMPs 对抗原的佐剂活性是它们被纳入疫苗的原因，并使制定“防御素疫苗”概念成为构建疫苗的创新基础成为可能。AMPs 的免疫调节功能涉及它们对最近微环境中细胞的影响、其他细胞的募集和激活，支持对致病微生物的反应并完成炎症过程，从而表现出全身效应。为了在医学实践中成功使用 AMPs，有必要详细研究它们的免疫调节活性，同时考虑到它们的多功能性。免疫系统和微环境的成熟度可以有助于预防并发症并提高治疗效果，因为 AMPs 在某些情况下可以抑制炎症，但在其他情况下会加重机体的反应和损伤。还应考虑到，一种或另一种 AMP 的实际功能取决于对靶细胞的总调节作用的类型，而不仅仅是单个肽的性质。广泛的生物活性，包括对病原体的直接作用、细菌毒素的失活以及对免疫活性细胞的影响，引起了研究人员的关注，然而，AMPs 对正常细胞的细胞抑制活性、其变应原性特性和对宿主蛋白酶的低稳定性，是 AMPs 医学应用的严重限制。在这方面，寻找选择性作用于靶标的化合物和开发适当的应用方法的任务变得至关重要。本综述的范围是总结天然和合成 AMPs 的免疫调节活性的最新概念和最新进展，并研究其医学应用的前景和限制。
